Methods and devices for coating stents

ABSTRACT

Various embodiments of methods and devices for coating stents are described herein.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a divisional of application Ser. No. 13/037,075,filed Feb. 28, 2011, now U.S. Pat. No. 8,691,320, which is a divisionalof application Ser. No. 11/764,006, filed Jun. 15, 2007, now U.S. Pat.No. 7,897,195, both of which applications are incorporated herein byreference.

BACKGROUND OF THE INVENTION

Field of the Invention

This invention relates to methods and devices for coating stents.

Description of the State of the Art

This invention relates to radially expandable endoprostheses, that areadapted to be implanted in a bodily lumen. An “endoprosthesis”corresponds to an artificial device that is placed inside the body. A“lumen” refers to a cavity of a tubular organ such as a blood vessel. Astent is an example of such an endoprosthesis. Stents are generallycylindrically shaped devices that function to hold open and sometimesexpand a segment of a blood vessel or other anatomical lumen such asurinary tracts and bile ducts. Stents are often used in the treatment ofatherosclerotic stenosis in blood vessels. “Stenosis” refers to anarrowing or constriction of a bodily passage or orifice. In suchtreatments, stents reinforce body vessels and prevent restenosisfollowing angioplasty in the vascular system. “Restenosis” refers to thereoccurrence of stenosis in a blood vessel or heart valve after it hasbeen treated (as by balloon angioplasty, stenting, or valvuloplasty)with apparent success.

Stents are typically composed of scaffolding that includes a pattern ornetwork of interconnecting structural elements or struts, formed fromwires, tubes, or sheets of material rolled into a cylindrical shape.This scaffolding gets its name because it physically holds open and, ifdesired, expands the wall of the passageway. Typically, stents arecapable of being compressed or crimped onto a catheter so that they canbe delivered to and deployed at a treatment site. Delivery includesinserting the stent through small lumens using a catheter andtransporting it to the treatment site. Deployment includes expanding thestent to a larger diameter once it is at the desired location.Mechanical intervention with stents has reduced the rate of restenosisas compared to balloon angioplasty. Yet, restenosis remains asignificant problem. When restenosis does occur in the stented segment,its treatment can be challenging, as clinical options are more limitedthan for those lesions that were treated solely with a balloon.

Stents are used not only for mechanical intervention but also asvehicles for providing biological therapy. Biological therapy usesmedicated stents to locally administer a therapeutic substance.Effective concentrations at the treated site require systemic drugadministration which often produces adverse or even toxic side effects.Local delivery is a preferred treatment method because it administerssmaller total medication levels than systemic methods, but concentratesthe drug at a specific site. Local delivery thus produces fewer sideeffects and achieves better results.

A medicated stent may be fabricated by coating the surface of a stentwith an active agent or an active agent and a polymeric carrier. Thoseof ordinary skill in the art fabricate coatings by applying a polymer,or a blend of polymers, to the stent using well-known techniques. Such acoating composition may include a polymer solution and an active agentdispersed in the solution. The composition may be applied to the stentby immersing the stent in the composition or by spraying the compositiononto the stent using various kinds of apparatus'. The solvent thenevaporates, leaving on the stent surfaces a polymer coating impregnatedwith the drug or active agent.

The accuracy of drug loading, the uniformity of the drug distribution,stent coating quality, and coating material selection are criticalfactors in making the drug eluting stent. Having a robust and costeffective drug eluting stent manufacturing process to enable goodcoating quality, high throughput, high yield, low machine down time isan important goal for coated stent manufacturers.

SUMMARY OF THE INVENTION

Various embodiments of the present invention include a device forcoating a stent comprising: a first support for supporting a firststent, the first support being coupled to a movable member; and a secondsupport for supporting a second stent, the second support being coupledto the movable member, the movable member configured to position one ofthe supports in a spraying zone and the other support in a drying zone,wherein the stent in the spraying zone can be spray coated while thestent in the drying zone is dried.

Further embodiments of the present invention include a method of coatinga stent comprising: applying a coating material to a first stent on afirst support positioned in a spraying zone of a device; and drying asecond stent supported on a second support while applying the coatingmaterial to the first stent, the second support positioned in a dryingzone of the device, wherein the device comprises a movable memberconfigured to position one of the supports in a spraying zone and theother support in a drying zone.

Additional embodiments of the present invention include a device forcoating a stent comprising: a spray nozzle disposed within a sprayingzone of a device; and a first support for supporting a first stent and asecond support for supporting a second stent, the first support and thesecond support being coupled to a member capable of positioning one ofthe supports in the spraying zone below the spray nozzle to receivecoating material from the spray nozzle and the other support in a dryingzone, wherein the spray nozzle is movable with respect to the support inthe spraying zone while the stent in the drying zone is drying, thespray nozzle being movable so that the support does not receive coatingmaterial.

Other embodiments of the present invention include a method of coating astent comprising: applying a coating material with a spray nozzlepositioned over a first stent supported on a first support positioned ina spraying zone; drying a second stent supported on a second supportwhile applying the coating material to the first stent, the secondsupport positioned in a drying zone; and shifting the spray nozzle awayfrom the first support to prevent further application of coatingmaterial on the first stent while the second stent is drying, the spraynozzle continuing to spray after shifting.

Certain embodiments of the present invention include a stent coatingdevice comprising: a rotatable support for supporting a stent, thesupport capable of rotating the stent about a cylindrical axis of thesupport; and a gripping mechanism positioned below the support capableof actuating upwards to apply a force to an outside surface of the stentto prevent rotation of the stent with respect to the support.

Further embodiments of the present invention include a method of coatinga stent comprising: applying a coating material to a stent mounted on arotatable support; applying a force to an outside surface of the stentwith a gripping mechanism; and rotating the support while the force isapplied to the outside surface of the stent, wherein the force preventsrotation of the stent with respect to the support.

Certain additional embodiments of the present invention include a devicefor coating a stent comprising: a spray nozzle for applying a coatingmaterial to a stent when the spray nozzle is positioned above the stent;a container for a solvent for cleaning the spray nozzle; and a movablesupport member coupled to the spray nozzle to move the spray nozzle froma position above the stent to a position above the container to allowcleaning of the spray nozzle with the solvent.

Additional embodiments of the present invention include a method ofcoating a stent comprising: spraying a coating material from a spraynozzle to coat a stent; moving the spray nozzle from a spraying positionabove the stent with a movable support member coupled to the spraynozzle to a position above a container to allow cleaning of the nozzlewith a solvent within the container; and contacting the spray nozzlewith the solvent within the container.

Certain other embodiments of the present invention include a method forcoating a stent comprising: feeding a gas and a liquid into a spraynozzle for coating a stent, the spray nozzle producing a spray plumefrom the gas and liquid fed to the nozzle; monitoring the gas flowproperties and the liquid flow properties prior to feeding the gas andliquid into the spray nozzle during the coating; and adjusting the gasflow properties and liquid flow properties to obtain selected flowproperties of gas and liquid into the spray nozzle, wherein theadjustment is based on the monitored gas and liquid flow properties.

Other embodiments of the present invention include a device for coatinga stent comprising: a spray nozzle for spraying a stent, the spraynozzle adapted to spray a spray plume produced from liquid and gas fedto the nozzle; a gas flow control system for monitoring and controllingthe flow of gas into the nozzle during the spraying; and a liquid flowcontrol system for monitoring and controlling the flow of liquid intothe nozzle during the spraying.

Further embodiments of the present invention include a support assemblyfor supporting a stent during coating comprising: a first supportelement with a proximal end disposed within a rotatable spindle; asupport wire extending from a distal end of the first support element,the proximal end of the support wire coupled to the distal end of thefirst support element; and a clamping element supporting a distal end ofthe support wire, wherein the proximal end and the distal end of the ofthe support wire are positioned so that the support wire rotatesconcentrically with the first support element when the first supportelement is rotated by the rotatable spindle.

Certain other embodiments of the present invention include a method ofcoating a stent comprising: calibrating a spray nozzle for coating astent so that a spray plume from the nozzle has selected properties;mounting the calibrated spray nozzle in a spray device, wherein a sprayplume from the mounted nozzle has the selected properties; and spraycoating a stent using the mounted spray nozzle.

Additional embodiments of the present invention include a device forcoating a stent comprising: a spray nozzle for applying a coatingmaterial; a drying nozzle for drying a coated stent; and a first stentsupport and a second stent support, the first stent support and thesecond stent support coupled to a movable member, the movable membercapable of positioning one of the stent supports for coating with thespray nozzle and the other stent support for drying with the dryingnozzle.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 depicts a three-dimensional view of a cylindrically-shaped stent.

FIG. 2 depicts an exemplary stent coating and drying device.

FIG. 3 depicts a close-up view of a baffle separating a spraying zoneand a drying zone in the device depicted in FIG. 1.

FIG. 4 depicts a close-up view of a spray zone of the device depicted inFIG. 1.

FIGS. 5A-B depict a close-up view of a drying zone of the devicedepicted in FIG. 1.

FIG. 6 depicts a close-up view of a cap fixture.

FIG. 7 shows a schematic side view of spray nozzle positioned above thecap fixture of FIG. 6.

FIGS. 8A-B depict embodiments for controlling the level of solvent in acap fixture.

FIG. 9A depicts a schematic diagram of a system for controlling theliquid and gas flow delivered to a spray nozzle.

FIG. 9B depicts a view of the device in FIG. 1 showing metering pumps.

FIG. 10 depicts a schematic of a spray nozzle above a stent.

FIGS. 11A-C depict close-up views of a stent support assembly forsupporting a stent during a spraying and drying process.

FIGS. 11D-E depicts an axial cross-section of a stents mounted onmandrels.

FIGS. 12A-C depicts a close-up view of the stent grippers from FIG. 1.

FIGS. 13-17 depict Scanning Electron Microscope images of a coatedstent.

DETAILED DESCRIPTION OF THE INVENTION

Embodiments of the present invention relate to coating implantablemedical devices such as stents. In particular, the embodiments of thepresent invention relate to aspects of methods and devices for spraycoating and drying stents.

More generally, embodiments of the present invention may also be used incoating devices including, but not limited to, self-expandable stents,balloon-expandable stents, stent-grafts, vascular grafts, cerebrospinalfluid shunts, pacemaker leads, closure devices for patent foramen ovale,and synthetic heart valves.

In particular, a stent can have virtually any structural pattern that iscompatible with a bodily lumen in which it is implanted. Typically, astent is composed of a pattern or network of circumferential andlongitudinally extending interconnecting structural elements or struts.In general, the struts are arranged in patterns, which are designed tocontact the lumen walls of a vessel and to maintain vascular patency. Amyriad of strut patterns are known in the art for achieving particulardesign goals. A few of the more important design characteristics ofstents are radial or hoop strength, expansion ratio or coverage area,and longitudinal flexibility. Embodiments of the present invention areapplicable to virtually any stent design and are, therefore, not limitedto any particular stent design or pattern. One embodiment of a stentpattern may include cylindrical rings composed of struts. Thecylindrical rings may be connected by connecting struts.

In some embodiments, a stent may be formed from a tube by laser cuttingthe pattern of struts in the tube. The stent may also be formed by lasercutting a metallic or polymeric sheet, rolling the pattern into theshape of the cylindrical stent, and providing a longitudinal weld toform the stent. Other methods of forming stents are well known andinclude chemically etching a metallic or polymeric sheet and rolling andthen welding it to form the stent.

In other embodiments, a metallic or polymeric filament or wire may alsobe coiled to form the stent. Filaments of polymer may be extruded ormelt spun. These filaments can then be cut, formed into ring elements,welded closed, corrugated to form crowns, and then the crowns weldedtogether by heat or solvent to form the stent.

FIG. 1 illustrates a conventional stent 10 formed from a plurality ofstruts 12. The plurality of struts 12 are radially expandable andinterconnected by connecting elements 14 that are disposed betweenadjacent struts 12, leaving lateral openings or gaps 16 between adjacentstruts 12. Struts 12 and connecting elements 14 define a tubular stentbody having an outer, tissue-contacting surface and an inner surface.

The cross-section of the struts in stent 10 may be rectangular- orcircular-shaped. The cross-section of struts is not limited to these,and therefore, other cross-sectional shapes are applicable withembodiments of the present invention. Furthermore, the pattern shouldnot be limited to what has been illustrated as other stent patterns areeasily applicable with embodiments of the present invention.

Coating a Stent

As indicated above, a medicated coating on a stent may be fabricated byspraying a coating composition including polymer and drug on the stent.Spray coating a stent typically involves mounting or disposing a stenton a support, followed by spraying a coating material from a nozzle ontothe mounted stent.

A spray apparatus, such as EFD 780S spray device with VALVEMATE 7040control system (manufactured by EFD Inc., East Providence, R.I.) can beused to apply a composition to a stent. An EFD 780S spray device is anair-assisted external mixing atomizer. The composition is atomized intosmall droplets by air and uniformly applied to the stent surfaces. Othertypes of coating applicators, including air-assisted internal mixingatomizers (such as IVEK SonicAir nozzle), ultrasonic applicators (suchas Accu-Mist nozzle or MicroMist nozzle from SonoTek Co. in Milton,N.Y.), or drop dispensing device can also be used for the application ofthe composition.

To facilitate uniform and complete coverage of the stent during theapplication of the composition, the stent can be rotated about thestent's central longitudinal axis. Rotation of the stent can be fromabout 0.1 rpm to about 300 rpm, more narrowly from about 30 rpm to about200 rpm. By way of example, the stent can rotate at about 150 rpm. Thestent can also be moved in a linear direction along the same axis. Thestent can be moved at about 1 mm/second to about 30 mm/second, forexample about 6 mm/second, or for a minimum of at least two passes(i.e., back and forth past the spray nozzle). In other applications, thespray nozzle can be devised to translate over the stent. The stent isrotated at a desired speed underneath the nozzle.

A nozzle can deposit coating material onto a stent in the form of finedroplets. An atomization pressure of a sprayer can be maintained at arange of about 5 psi to about 30 psi. The droplet size depends onfactors such as viscosity of the solution, surface tension of thesolvent, solution feed rate, and atomization pressure. The flow rate ofthe composition from the spray nozzle can be from about 0.01 mg/secondto about 1.0 mg/second, for example about 0.1 mg/second. Only a smallpercentage of the composition that is delivered from the spray nozzle isultimately deposited on the stent depending on the transfer efficiencyof the spray setup. By way of example, when a composition is sprayed todeliver about 1 mg of solids, only about 100 micrograms or about 10% ofthe solids sprayed will likely be deposited on the stent. The solidpercent in the composition typically can range from 0.1 wt % to 15 wt %,for example about 5 wt %.

To reduce or eliminate coating defects in coated stents, excessivesolvent is removed from applied coating material through an in-processdrying cycle. Excessive application of the polymer or excessive solventleft in the coating can cause coating defects such as pool web(excessive material accumulated between stent struts) due to the lack ofgood wettability of the coating droplets over a stent with a tightgeometry.

To avoid excessive application of coating material, the coating processcan involve multiple repetitions of spraying forming a plurality oflayers. A repetition can involve a single pass or multiple passes ofmoving a spray nozzle (or moving the stent), a pass being from one end(e.g., proximal end) to the other end (e.g., distal end) of a stent.Each repetition can be, for example, about 0.5 second to about 20seconds, for example about 10 seconds in duration. The amount of drycoating applied by each repetition can be about 1 microgram/cm² (ofstent surface) to about 75 micrograms/cm², for example, less than about20 micrograms/cm².

As indicated above, the coating composition can include a polymer and adrug dissolved in a solvent. Each repetition can be followed byin-process drying involving removal of a significant amount of thesolvent(s). In an embodiment, there may be less than 5%, 3%, or morenarrowly, less than 1% of solvent remaining in the coating afterin-process drying between repetitions. When the coating process iscompleted, all or substantially all of the solvent may be removed fromthe coating material on the stent. Any suitable number of repetitions ofapplying the composition followed by removing the solvent(s) can beperformed to form a coating of a desired thickness or weight. Excessiveapplication of the polymer can, however, cause coating defects.

A stent coated with coating material can be dried by allowing thesolvent to evaporate at room or ambient temperature. Depending on thevolatility of the particular solvent employed, the solvent can evaporateessentially upon contact with the stent. Alternatively, the solvent canbe removed by subjecting the coated stent to various drying processes.Drying time can be decreased to increase manufacturing throughput byheating the coated stent. For example, removal of the solvent can beinduced by baking the stent in an oven at a mild temperature (e.g., 60°C.) for a suitable duration of time (e.g., 2-4 hours) or by theapplication of warm air. There can be some residual solvent left in thecoating after the in-process drying depending on the solvent used andin-process drying time. The higher the boiling point of the solvent, theharder it is to remove solvent in the in-process drying process. Thecoated stent is typically dried in an oven as the final drying step whenthe multiple deposition stages are completed to remove residual solvent.The residual solvent can have harmful biological effects andplasticizing effects which can alter the release rate and coatingproperties. The energy source of the oven can range from a conventionaloven to an infrared oven or UV.

Evaporation of the solvent(s) can be induced by application of a warmgas between each repetition which can prevent coating defects andminimize interaction between the active agent and the solvent. The stentmay be positioned below a nozzle blowing a warm gas. A warm gas may beparticularly suitable for embodiments in which the solvent employed inthe coating composition is of a low volatility (e.g., dimethylsulfoxide(DMSO), dimethylformamide (DMF), and dimethylacetamide (DMAC)). Thetemperature of the warm gas can be from about 25° C. to about 200° C.,more narrowly from about 40° C. to about 90° C. By way of example, warmgas applications can be performed at a temperature of about 60° C., at aflow speed of about 5,000 feet/minute, and for about 10 seconds.

The gas can be directed onto the stent following a curing period ofabout 3 seconds to about 60 seconds, more narrowly for about 10 secondsto about 20 seconds, so as to allow the residual solvent(s) to beremoved to form a coating. The curing period is particularly short ifthe coating composition contains a volatile solvent since such solventsare typically removed quickly. As used herein “volatile solvent” means asolvent that has a vapor pressure greater than 17.54 Torr at ambienttemperature, and “non-volatile solvent” means a solvent that has a vaporpressure less than or equal to 17.54 Torr at ambient temperature.

Any suitable gas can be employed, examples of which include air, argon,or nitrogen. The flow rate of the warm gas can be from about 20 cubicfeet/minute (CFM) (0.57 cubic meters/minute (CMM)) to about 80 CFM (2.27CMM), more narrowly about 30 CFM (0.85 CMM) to about 40 CFM (1.13 CMM).The warm gas can be applied for about 3 seconds to about 60 seconds. Byway of example, warm air applications can be performed at a temperatureof about 50° C., at a flow rate of about 40 CFM, and for about 10seconds.

Embodiments of the present invention may be illustrated by the exemplaryspray coating device 200 depicted in FIG. 2, which shows a front view.Device 200 is configured to process two stents simultaneously. However,device 200 can process only one stent if desired. Device 200 has aspraying zone 202 and a drying zone 204, which enable coating of onestent and drying of another stent simultaneously. Stent supportassemblies 208 and 222 can be moved between spraying zone 202 and dryingzone 204 via a rotating drum to allow simultaneous spraying of a stenton one stent support assembly and drying of another stent on anotherstent support assembly.

Spraying zone 202 has a spray nozzle 206 that is mounted above movablestent support assembly 208. Stent support assembly 208 is inserted intoa spindle which is connected to a gear system that is powered by a motor(not shown) which provides rotational motion to the stent supportassembly 208, as depicted by an arrow 242, during the coating process.Hose 210 feeds gas to spray nozzle 206 and liquid coating material isfed to spray nozzle 206 via port 212. A tubing or line (not shown) canconnect port 212 to a liquid coating material source. Spray nozzle 206is translatable along a y-direction, as shown by double-headed arrow205, along the axis of stent support assembly 208. Spray nozzle 206 isalso movable along an x-direction as shown by an arrow 207.

Spraying zone 202 includes upper funnel 214A and lower funnel 214B.Lower funnel 214B is connected to an evacuation system that creates avacuum at funnel 214A and 214B to collect excess coating materialgenerated from the overspray. The evacuation system can be on during allor part of the coating process. A wetcap device 216, described in moredetail below, adjacent to upper funnel 214A is for cleaning the tip ofspray nozzle 206.

Spray nozzle 206 is dwelled in a nozzle holder 220 which is attached toa mounting bracket block 218. Mounting bracket block 218 is coupled to alinear slide that can control movement of nozzle holder 220 and spraynozzle 206 back and forth in the x-direction during the application ofthe coating material over the stent. Mounting bracket block 218 is alsocoupled to a sliding stage to enable nozzle holder 220 along with spraynozzle 206 to side shift back and forth in the y-direction to a positionover upper funnel 214A after a spray cycle is complete. Theside-shifting of nozzle holder 220 along with spray nozzle 206 clearsthe path in the spray zone to allow the drum to rotate to advance thestent at the drying zone 204 to the spraying zone 202 to receive coatingmaterial. The side shift motion clears the path in the spray zone toallow the drum to rotate, advancing the stent at the drying zone to thespray zone to receive to more coating material.

Drying zone 204 includes a drying nozzle 224 that can be positioned overa movable stent support assembly 222 for supporting a coated stentduring drying. Stent support assembly 222 is inserted into a spindlewhich is connected to a gear system that is powered by a motor (notshown) which provides rotational motion to the stent support assembly222, as depicted by an arrow 243, during the drying process. In someembodiments, the same motor provides rotational motion to stent supportassemblies 208 and 222. Drying nozzle 224 includes an electrical heater230 to generate heated air for drying nozzle 224. Drying nozzle 224 ismovable and can shift in an x-direction, as shown by a double-headedarrow 245, from its position shown in FIG. 2 to a drying position overstent support assembly 222. Drying nozzle 224 can be positioned abovestent support assembly 222 so that it can dry a stent coated in sprayingzone 202 by blowing warm gas over a freshly coated stent. Stent grippers250 and 252 for clocking a stent, as described in detail below, aredisposed below stent support assembly 222.

Movement of mounting bracket 220, and thus, nozzle 206, is accomplishedby motors (not shown). Shifting of drying nozzle 224 is performed bymotors (not shown). The motors can be controlled by a controller thathas pre-programmed instructions on the movement of nozzles 206 and 224.

The side shift of drying nozzle 224 and spray nozzle 206 may beaccomplished with pneumatic slides or motor driven linear slides. Theside-shift of the drying nozzle allows the indexing drum to rotate, butalso accommodates differences in the drying time and the spraying time.The side-shift of drying nozzle 224 results in a deflection of thedrying air away from the stent to prevent over-drying while the otherstent is finishing its spray cycle. Thus, the spray cycle and dry cycleare not limited to the same duration for process flexibility.

Stent support assemblies 208 and 222 are supported at their distal endsby clamps 226 and 227, respectively. The proximal end of stent supportassembly 222 is shown to be supported by a spindle or end cap 228. Thedistal end of stent support assembly 208 is supported in the samemanner, but is hidden by spray nozzle 206. End cap 228 is mounted orcoupled on a rotatable drum 240 which rotates as shown by arrow 232.Rotatable drum 240 can rotate to reverse the position of stent supportassemblies 208 and 222 so that stent support assembly 208 is in dryingzone 204 and stent support assembly 222 is in the spray zone 202.

The scissor-type end supports facilitate automatic loading/unloading ofparts to the spindles. Since the supports are mounted to a baffle 244,ends of the mandrels are supported during the indexing of the drum. Thisprevents oscillation of the core wires with collets which could damagethe coating. Such oscillation would limit the acceleration/decelerationof indexing of the drum.

In some embodiments, device 200 can be used as part of an automatedprocess. Robotic arms (not shown) can position a shaft of stent supportassemblies 208 and 222 that include an uncoated stent within holes inendcaps or spindles. After coating is completed, the robotic arm canremove the stent support assemblies from the endcaps or spindles.Gripping collets inside the spindles can be opened and closedautomatically to allow automated loading/unloading of parts.

Spray zone 202 and drying zone 204 are separated by baffle 244 which ismounted on a back plate 248 of rotatable drum 240. Baffle 244 isconfigured to reduce or eliminate heat and mass transfer between sprayzone 202 and drying zone 204. In particular, baffle 244 reduces orprevents coating material sprayed from nozzle 206 from contacting astent that is being dried in drying zone 202. Additionally, baffle 244acts as a thermal barrier that reduces or prevents conductive orconvective heat transfer between spray zone 202 and drying zone 204. Inparticular, baffle 244 reduces or prevents conductive heat transfer tospraying zone 202 due to heated gas from drying nozzle 224. Baffle 244also blocks air currents that may carry coating material to drying zone204 or heated air to spraying zone 202.

Baffle 244 can be fabricated of materials that provide thermalinsulation between spraying zone 202 and drying zone 204. In addition,such materials should also maintain thermal and mechanical propertiesduring the spraying and coating process. For example, the materialsshould be insoluble in the solvent(s) used in the coating material andshould be resistant to significant changes in properties caused by theheat from drying nozzle 224. For example, baffle 244 can be fabricatedat least in part of a polymeric or plastic material. A close-up view ofbaffle 244 is provided in FIG. 3. Baffle 244 is a composite structurehaving two outer polymer plates 302 and 304 that provide thermalinsulation. Baffle 244 has an inner metallic support 306 to provide arigid structural support to baffle 246. Metallic layer 306 has channelsor voids 308 to reduce the heat conduction through baffle 244 and whichalso provides the required space to accommodate an end support mechanismto the stent support assemblies to improve the alignment of theassemblies to the nozzles as illustrated in FIG. 11C. In an exemplaryembodiment, baffle 244 has outer layers fabricated frompolyetheretherketone (PEEK) and an inner layer of stainless steel. Thestructure of baffle 244 is not limited to that depicted in FIG. 3.

As indicated above, it is desirable to coat stents with multiplespray/dry cycles Device 200 is designed to allow spraying of stent inspray zone 202 while a coating layer previously applied at spray zone202 is dried at drying zone 204. Simultaneous spraying and dryingreduces or eliminates idle time of sequential spraying and dryingoperation, thus increasing the throughput of a coating operation.

Specifically, a layer of coating material is applied to a first stentmounted on stent support assembly 208 by spray nozzle 206. At the sametime, a second stent mounted on stent support assembly 222 with coatingmaterial already applied in spray zone 202 is dried by drying nozzle224. When both the spray coating on the first stent and drying of thesecond stent are completed, rotatable drum 240 rotates and positions thesecond stent (dried) at spray zone 202 and the first stent (freshlycoated) at drying zone 204. The first stent may then be dried at dryingzone 204 and a layer of coating material can be applied to the secondstent at spray zone 202. The spraying and drying can be repeated aselected number of times necessary to obtain a desired coating mass oneach of the stents. Rotatable drum 240 can rotate clockwise orcounterclockwise to change the position of the first stent and secondstent between spray zone 202 and drying zone 204. The motion ofrotatable drum 240 can be controlled by a belt driven gear assembly (notshown) which is powered by a motor (not shown). Stent support assembly208 and stent support assembly 222 are rotated in each spraying anddrying cycle. As shown by arrow 232, the first stent is rotated to sprayzone 202 and the second stent is rotated to drying zone 204, and afterthe spraying/drying cycle is complete the first stent is rotated back todrying zone 204 for drying the stent and the second stent is rotated tospray zone 202 to receive coating material.

To allow rotation of rotatable drum 240 when both the spray coating of afirst stent and drying of a second stent are completed, spray nozzle 206shifts away from stent support assembly 208. In addition, drying nozzle224 can also shifts away from stent support assembly 222 to allowrotation of rotatable drum 240.

A close-up view of spray zone 202 is shown in FIG. 4. Spray nozzle 206can shift in an x-direction to a position over upper funnel 214A, asshown by an arrow 402. As indicated above, spray nozzle 206 translateslinearly along the y-axis, as shown by an arrow 404, of stent supportassembly 208 during application of coating material to a stent mountedon stent support assembly 208. Spray nozzle 206 can side shift in thex-direction to be positioned over upper funnel 214A after the spraycycle is complete and spray nozzle 206 can rest at any position alongthe y-axis over funnel 214A to await the next spray cycle. Spray nozzle206 can continue spraying or turn off while it is waiting, or it canadvance to the wetcap device 216 for wet-capping to clean the nozzletip.

FIGS. 5A-B depict a close-up view of drying zone 204. Drying nozzle 224is shown shifted away from a position above stent support assembly 222,as shown by an arrow 502, to a position as shown. A temperature probe504 with a sensoring zone 506 at its tip extends outward toward dryingnozzle 224. Temperature probe 504 monitors the temperature of warm gasstream exiting from drying nozzle 224. Temperature probe 504 is coupledto a housing 509. The housing 509 and drying nozzle 224 are bothattached to a linear stage which enables and maintains the alignment ofdrying nozzle 224 to temperature probe 504. Temperature probe 504 anddrying nozzle 224 move back and forth along the x-direction so thattemperature probe 504 remains a fixed distance from drying nozzle 224and can continue to monitor the temperature of the warm gas stream.

FIG. 5B shows a slotted opening 510 through which warm gas passes fordrying a coated stent mounted on stent support assembly 222. A deflectorshield 508 is positioned below drying nozzle 224 in its right-mostshifted position. Deflector shield 508 deflects the warm gas streamexiting drying nozzle 224 to the downstream evacuation when dryingnozzle 224 is shifted away from stent support assembly 222 when thedrying cycle is complete. Perforated plates or screens 516 can beincorporated into drying nozzle 224 to improve the mixing of the hot gasexiting from the heating element (not shown) located at the upperportion of drying nozzle 224 to provide an air stream with a uniformtemperature distribution.

The time for drying a stent with drying nozzle 224 can be different fromthe time for spraying a layer of coating material on a stent with spraynozzle 206. In some embodiments, spraying nozzle 206 can finish acoating layer on a stent mounted on a stent support assembly prior to astent mounted on a stent support assembly is finished drying. In oneembodiment, the flow of coating material from spray nozzle 206 can bestopped after completing the deposition of a layer on a first stent inspraying zone 202. The spraying and drying can be started again afterrotatable drum 240 has rotated and positioned the stent from the dryingzone in spraying zone 202 and the freshly coated stent in drying zone204.

A potential disadvantage of stopping the flow of coating material isnozzle fouling which refers to residual coating material in the nozzledrying up and reducing or preventing flow of coating material throughthe nozzle. Nozzle fouling can degrade the nozzle performance and it canreduce the coating weight consistency and coating quality. In analternative embodiment, spray nozzle 206 can continue to spray coatingmaterial even after completing deposition of a coating layer on a stentin spraying zone 204 to minimize nozzle fouling. Spray nozzle 206 canshift in the x-direction to a position away from the coated stent sothat no additional coating material is applied to the stent. Spraynozzle 206 can be positioned adjacent to or above funnel 214 aftercompleting deposition to prevent further deposition of coating materialon the stent. The evacuation system (not shown) creates a vacuum atupper funnel 214A and removes all or a substantial portion of thecoating material that continues to be sprayed from spray nozzle 206.

As described above, a wetcap device 216 shown in FIG. 2 is provided forcleaning the tip of spray nozzle 206. Wetcap device 216 can removecoating material that may have accumulated at the tip of spray nozzle206 by using a solvent that can soften or dissolve the build-up ofcoating material at the nozzle tip. FIG. 6 depicts a close-up view ofwetcap device 216. Wetcap device 216 has an opening or solvent well 602to allow the solvent, supplied from an external solvent supply system(not shown) to form a meniscus to allow the material build up at thenozzle tip to be dissolved or to be softened. In one embodiment, thesolvent is the same as the solvent used in the coating material. Toclean the tip of spray nozzle 206 with wetcap device 216, spray nozzle206 is shifted in the x-direction, y-direction, or a combination of bothso that it is positioned above opening 602 of cap fixture 216. Capfixture 216 is configured to move upward in the z-direction, as shown byan arrow 604. Cap fixture 216 is moved upward an amount sufficient forthe tip of spray nozzle 206 is immersed in solvent well 602 in thechamber.

FIG. 7 shows a schematic side view of spray nozzle 206 positioned abovecap fixture 216 that contains a solvent 702. As shown by arrow 604, capfixture 216 can shift upward so that tip 704 of spray nozzle 206 isimmersed in solvent 702. Nozzle tip 604 remains immersed in the solventa sufficient period of time to remove coating material from the tip.After cleaning of nozzle tip 704, cap fixture 216 is lowered and spraynozzle 206 is shifted back into a position for spraying a stent.

Nozzle tip 704 can be cleaned with cap fixture 216 at any time there isa lapse in spraying, i.e., between applications of a coating layer or arepetition. Specifically, nozzle tip 704 can be cleaned at cap fixture216 to prior and/or during reversing the positions of stent supportassemblies 208 and 222 with rotation drum 240. Nozzle tip 704 can becleaned after every coating layer/repetition or at any frequency ofcoating layers. In one embodiment, nozzle tip 704 is cleaned when thecoating of the two stents is completed. Nozzle tip 704 can be cleanedwhile the coated stents are removed from stent support assemblies 208and 222 and uncoated stents are mounted on the stent support assemblies.

It is important for the solvent well 602 in cap fixture 216 to be filledwith enough solvent enough so that nozzle tip 704 is immersed in thesolvent when cap fixture 216 shifts upward. The level of solvent in capfixture 216 can change with time due to evaporation of the solvent. Itmay be necessary to continuously or periodically monitor the level ofsolvent in cap fixture 216 to maintain the level of solvent so thenozzle tip is immersed when cap fixture 216 is raised.

Various methods can be used to control the level of solvent in capfixture 216 so that nozzle tip 704 is immersed when cap fixture 216 isshifted upwards. Exemplary embodiments are depicted in FIGS. 8A-B. Theembodiment in FIG. 8A includes a conductivity loop 802. Conductivityloop 802 has at one end an electrical lead 804 positioned at a desiredlevel of solvent in cap fixture 216. At another end of conductivity loop802, an electrical lead 806 is positioned in cap fixture 216 belowelectrical lead 804. An electrical current is passed throughconductivity loop 802 from current source 808. A resistometer 810monitors changes in resistance in conductivity loop 802. Conductivityloop 802 remains closed as long as the level of solvent remains at orabove the position of electrical lead 804. When the level of solvent incap fixture 216 goes below the position of electrical lead 804,resistometer 810 detects an open loop due to an increase in resistance.Resistometer 810 is in communication with a pump 812. Pump 812 canreceive a signal from resistometer 810 which causes pumping of solventfrom a solvent reservoir 814 into cap fixture 216 until the level ofsolvent in cap fixture 216 is restored to the level of electrical lead804. Pump 812 can be configured to stop pumping solvent when it receivesa signal from resistometer 810 of a decrease in resistance due toclosing of conductivity loop 802.

In a similar manner, a conductivity loop can be between electrical lead804 and nozzle tip 704. The continuity of this conductivity loop detectswhether the tip of the nozzle is in the solvent. Such a loop accountsfor a low solvent level as well whether the nozzle tip is mis-alignednozzle to the solvent pool.

Another method of controlling the level of solvent in cap fixture 216,illustrated in FIG. 8B, includes reducing the level of solvent from adesired level 804 to a level 816. The level can be reduced by pullingsolvent to an external reservoir. Reducing the level of solvent to level816 can be determined by a detector 818 positioned at level 816 thatdetects a meniscus. Detector 818 can be an ultrasonic detectormanufactured by Cosense, Inc. of Hauppauge, N.Y. The amount of solventremoved can be measured, and, therefore, is known. Prior to anothernozzle tip cleaning, the known amount of fluid can be metered and pumpedback into cap fixture 216 to restore the level of solvent to level 804.

Additionally, the presence of bubbles in the solvent anywhere in thedevice is undesirable, including within cap fixture 216. An ultrasonicsensor 820 positioned within cap fixture 216 can be used to detect thepresence of bubbles. If the bubble volume is larger than a selectedvalue, then the wet cap system can be purged by removing the solvent andreplaced with fresh solvent.

After the spray nozzle shifts aways from wetcap device 216 to funnel214A, spray nozzle 206 can be programmed to be purged over funnel 214Aat selected times and rates prior to the restart of the coating process.

A number of parameters influence the magnitude and consistency of themass per pass of coating material applied by a spray nozzle and coatingquality, in general. These parameters include the mass flow rate of gasand liquid feed to spray nozzle 206 shown in FIG. 2, the liquid/gasratio fed to spray nozzle 206, the distance between the spray nozzle anda stent supported on a stent support assembly, the rotation rate of astent support assembly, and the translation rate of spray nozzle 206.The liquid/gas ratio is critical since it determines the size ofdroplets produced by the spray nozzle. As the liquid/gas ratioincreases, the size of the droplets increases. Device 200 allowsadjustment of each of the parameters to obtain a desired mass per passand coating quality.

In particular, it is important for the mass flow rate of liquid and gasto remain at selected levels throughout coating process so that theamount of coating material deposited per pass remains constant. As aresult, the overall mass of coating material deposited on the stent isconsistent and predictable from stent to stent.

In some embodiments, device 200 controls the flow of gas and liquid witha closed loop continuously monitored system. Device 200 can includeintegrated components for control of the mass flow rate of the liquidand gas delivered to spray nozzle 206. As discussed above, liquidcoating material and gas are fed into spray nozzle 206. Liquid coatingmaterial is fed into port 212 through a hose or tubing (not shown) andgas is fed through hose 210.

FIG. 9A depicts a schematic diagram of a system 900 of components forcontrolling the liquid and gas flow delivered to spray nozzle 206. Thegas flow line of system 900 includes a gas source 902, pressureregulator 904, mass flow controller 906, and pressure transducer 908.Liquid coating material is delivered from a liquid source 910 bymetering pumps 912 and 914 to spray nozzle 206. The liquid and gas meetat the tip of nozzle 206, and the liquid drop is broken up into smallerdroplets by the gas (so-called atomization process). FIG. 9B depicts aclose-up view of device 200 showing metering pumps 912 and 914 for theliquid coating material.

Mass flow controller 906 maintains a selected mass flow rate of gas andpressure transducer 908 monitors the gas pressure in the gas line tospray nozzle 206. Mass flow controller 906 monitors and controls themass flow rate of gas passed through mass flow controller 906 tomaintain the mass flow rate of gas delivered to spray nozzle 206. Massflow controller 906 can compensate for an increase or decrease in massflow rate of gas due to the pressure difference that occurs betweenvalve 904 and the location in the gas line of mass flow controller 906.A decrease in mass flow rate can be caused, for example, by frictionallosses. Mass flow controller 906 can be any suitable commerciallyavailable gas mass flow controller, for example, a thermal mass flowcontroller. An example of a commercially available mass flow controlleris MC20A high flow mass controller from MKS Instruments, Inc. Mass flowcontroller 906 can include a valve which adjusts the flow rate based ondetected changes in the flow rate of gas.

Pressure transducer 908 is positioned in the gas line between mass flowcontroller 906 and spray nozzle 206. Positive departures in the pressurecan be caused by, for example, blockage of the nozzle by coatingmaterial or blockage due to kinked hoses. Negative departures in thepressure may be due to leaks, for example, resulting from loosefittings. Pressure transducer 908 monitors pressure in the gas line forchanges in pressure and is in communication with valve 904 through acontroller 909. A selected change in backpressure detected by pressuretransducer 908 is compensated for through a control signal fromcontroller 909 to pressure valve 904.

Metering pumps 912 and 914 deliver a selected flow rate of liquid tospray nozzle 206. Pumps 912 and 914 precisely meter liquid to spraynozzle 206. Pumps 912 and 914 act in tandem to allow precise meteringand to enable continuous spraying. As one pump is dispensing the liquidto nozzle 206, the other pump is aspirating liquid from reservoir 910.The use of two pumps in tandem is an advantage over a single larger pumpsince the smaller the pump, the more accurate the dispensing of a smallamount of liquid to the nozzle.

Additionally, as indicated above, the presence of bubbles in the liquidline is generally undesirable. The presence of bubbles tends to cause anegative departure from the desired mass of coating material depositedon the stent by spray nozzle 206. Bubbles in the pumps 912 and 914 alsoreduce the accuracy of the mass of liquid coating material dispensed bythe pumps. Bubbles can be generated, for example, through the aspiratingof pumps 912 and 914. The more volatile the solvent, the greater is thepropensity of a pump to generate bubbles during aspirating. Bubbledetectors can be positioned at any point along the liquid line as shownby bubble detectors 916, 918, and 920. Bubble detectors 916, 918, and920 can monitor the volume of bubbles in the liquid coating material. Ifthe detected volume is greater than a selected tolerance, a signal canbe generated by a control system to communicate an alarm and/or takecorrective action. Corrective action can include purging the liquidline, pumps, inspecting any leakage from the line, and/or reservoir ofsolvent.

In some embodiments of device 200 shown in FIG. 2, a distance betweeneither or both spraying nozzle 206 or drying nozzle 224 and a stentsupport assembly can be adjustable. Spraying nozzle 206 can be coupledto mounting bracket 220 via a screw that allows the distance between thenozzle and the stent support assembly to be varied. Drying nozzle 224 ismounted in a similar manner. Referring to FIG. 10, with respect tospraying, a height (H_(S)) above a stent 1001 is a process parameterthat can be used to control the mass per mass deposited on stent 1001.The density and size of the droplets in a spray plume 902 varies withH_(S). Therefore, H_(S) influences the characteristics of a resultantcoating. Furthermore, the distance between the drying nozzle 224 and astent support assembly is an additional drying process parameter inaddition to gas stream temperature and flow rate.

In further embodiments, either or both spray nozzle 206 or drying nozzle224 are detachable from device 200. Spraying nozzle 206 is detachablefrom all connections with device 200. Spraying nozzle 206 can bereleasably coupled to mounting bracket 220 by various types of mountingmechanisms known in the art, for example, dovetail connectors, butterflyconnectors, nuts and bolts, etc. Drying nozzle 224 can also bereleasably coupled in a similar manner to a mounting bracket (notshown). Gas feed hose 210 and liquid feed line that feeds liquid coatingmaterial into port 212 can also have quick-connect couplings to spraynozzle 206.

Such known connection mechanisms can be configured to allow the mountingand positioning of a nozzle in a repeatable manner, i.e., a nozzle canbe placed in the same position each time it is mounted. The releasableconnections allow spray nozzle 206 and drying nozzle 224 to be liftedout and inserted back into device 200 in to a designated position withrespect to stent support assemblies 208 and 222.

A spray nozzle for coating a stent can be assembled and calibratedexternal to device 200. For example, a spray plume from the nozzle canbe calibrated so that it has selected properties. The selectedproperties can include, but are not limited to, a selected flowdistribution that corresponds to a liquid and gas flow rate into thenozzle. The flow distribution can include the velocity or density ofdroplets as a function of distance from the nozzle tip. The calibratedspray nozzle can then be mounted in spray device 200 such that a sprayplume from the mounted nozzle has the selected properties.

The detachability and repeatability are particularly important whendevice 200 is used in an automated fashion. Additionally, detachabilityand repeatability allows rapid replacement of spray or dry nozzles withclean nozzles or nozzles more appropriate for different applications.Detachability of a spray nozzle for cleaning away from device 200reduces idle time of device 200.

It is important for the drying process to be performed in a consistentmanner for each layer and each stent. The same or similar processingconditions or parameters should exist for each layer of coating materialapplied for each stent. Drying process parameters can influence themolecular structure and morphology of a dried polymer and drug coating.Drug release parameters depend upon on molecular structure andmorphology of a coating. Therefore, drug release parameters depend uponparameters of the drying process. For example, generally, the rate of adrying process is directly proportional to the resultant drug releaserate of a resultant coating.

Since the temperature of a drying process is directly related to therate of drying, it is important to control the drying temperature toobtain coating consistency. In general, the more consistent thetemperature during the drying process from layer to layer and stent tostent, the more consistent the resultant coating in a given stent andfrom stent to stent.

The temperature of a warm gas stream that is used to dry a stent may beadjusted by controlling the heat supplied by electrical heater 230,depicted in FIG. 2. Temperature sensor 506 shown in FIGS. 5A-B ispositioned adjacent to a stent supported by a stent support assembly tomeasure the drying temperature of the applied coating. Temperaturesensor 506 is positioned as close as possible to stent withoutsignificantly disrupting the flow of heated fluid past the stent. In oneembodiment, there is no or substantially no offset or difference intemperature between the drying temperature of the coating on the stentand the temperature measured by sensor 506. In other embodiments, sensor506 is positioned far enough away so that there is an offset in themeasured temperature and the drying temperature. Such an offset can betaken into account in a control system described below. Temperaturesensor 506 can be a thermistor, thermocouple, or any other temperaturemeasuring device.

Temperature sensor 506 measures the drying temperature to gatherfeedback (T_(F)) for controlling the drying temperature of a stentmounted on a stent support assembly. Sensor 506 is coupled to a controlsystem by a sensor wire. Any suitable control system, such as a closedloop system, can be used for maintaining the drying temperature of thecoating at a desired temperature (T_(D)). A temperature, T_(F), measuredby sensor 506 is transmitted to the control system. The control systemcompares T_(F) to T_(D) and then transmits a signal to electrical heater230. The signal carries instructions to heater 230 to adjust thetemperature of the warm gas stream supplied from drying nozzle 224 ifthe difference in temperature is larger than a selected tolerance. Insome embodiments, the desired temperature T_(D) can be a function ofdrying time or coating thickness.

As described above, device 200 includes stent support assemblies 208 and222. In general, a stent can be supported on a mandrel or rod thatsupports the stent along its length by positioning the stent over themandrel. A stent can also be supported at its ends with supports havinga variety of geometries, such as supports with tapered or untaperedends. Thus, the present invention is not limited to the stent supportsdisclosed in the present application.

FIGS. 11A-C depict close-up views of a stent support assembly forsupporting a stent during a spraying and drying process. The stentsupport assembly has a distal portion or shank 1102. A portion of shank1102 is secured within a cylindrical hole in spindle or end cap 228which rotates, as shown by an arrow 1103A in FIG. 11B in FIG. 11C, torotate the stent support assembly, as shown by an arrow 1103B, duringcoating and drying of a stent mounted on the stent support assembly. Thestent support assembly further includes a mandrel cone 1104 forsupporting a distal end of a stent and a mandrel cone 1105 forsupporting a proximal end of the stent. As shown in FIG. 11A, a corewire 1106 extends from the tip of mandrel cone 1104 and through a collet1108 with a mandrel cone space 1105. Mandrel cones 1104 and 1105 canhave a roughened surface to absorb excess coating material. A stent 1123is shown supported by mandrel cones 1104 and 1105 over core wire 1106.

Core wire 1106 has a diameter less than a stent. For example, core wire1106 has a diameter between about 0.010″ and 0.030″. Core wire 1106 canbe made of a metallic material such as Nitonol wire which can providegood dimensional stability and rigidity.

As shown in FIG. 11B, core wire 1106 is supported at a proximal end by atailstock support 1112. Tailstock support 1112 is a scissor-likemechanism with two movable flat extension arms 1114 and 1116 that canopen as shown by arrows 1118 and 1120, respectively. Flat extension arms1122 and 1124 with opposing wedge- or v-shaped cut-out sections arecoupled to distal ends of movable extended arms 1114 and 1116,respectively. Arms 1114 and 1116 are coupled to baffle 244 by a supportfixture 1130 that is coupled to baffle 244. Support fixture 1130 iscomposed of two end plates 1132 (outer) and 1134 (inner) that are usedto house and support flat extension arms 1114 and 1116. Proximal ends ofextension arms 1114 and 1116 (one from drying zone 204 and one fromspray zone 202) are connected to two bars (one at an upper location andone at a lower location) which are linked to an air cylinder to pullthem up or down to close or open the tailstock support.

The proximal end of core wire 1106 is clamped at the apices 1138 and1140 of the opposing wedge-shaped cut-out sections of plates 1122 and1124. Therefore, the stent support assembly can be rotated with littleor no deviation of core wire 1106 from the rotational axis. Tailstocksupport 1112 prevents any excessive movement at the distal end of corewire 1106 as it rotates about its axis and during rotation of rotatabledrum 240.

As shown in FIG. 11D, a stent 1123 can be mounted between mandrel cones1104 and 1105 to obtain 1:1 rotation between stent 1123 and mandrelcones 1104 and 1105. The gap between the end rings of stent 1123 andmandrel cones 1104 and 1105 can be adjusted to provide an optimalcontact force to assure that mandrel cones 1104 and 1105 and stent 1123have the same or substantially the same axes of rotation.

However, the exerted force should not compress stent 1123 so as todistort the body of stent 1123. Over or under application of supportforce can lead to problems such as stent 1123 resting too loosely on thestent support assembly, stent 1123 bending, opposing ends of stent 1123flaring on mandrel cones 1104 and 1105, and increased contact betweenstent 1123 and mandrel cones 1104 and 1105, all of which can lead tocoating defects.

In other embodiments, a stent does not have a 1:1 rotation withsupporting end elements such as mandrel cones 1104 and 1105. As shown inFIG. 11E, stent 1123 can be mounted on mandrel cones 1104 and 1105 sothat stent 1123 and mandrel cones 1104 and 1105 have a different axis ofrotation. Mandrel cones 1104 and 1105 have an axis of rotation x_(M) andstent 1123 has an axis of rotation x_(S) longitudinally through itscenter. Thus, the contact points or area between mandrel cones 1104 and1105 and stent 1123 continuously change.

Another aspect of the present invention relates to reducing oreliminating coating defects that can result from stent contact withsupports, such as mandrels, during coating. While some coating defectscan be minimized by adjusting the coating parameters, other defectsoccur due to the nature of the interface between the stent and theapparatus on which the stent is supported during the coating process.Surface contact between the stent and the supporting apparatus canprovide regions in which the liquid composition can flow, wick, andcollect as the composition is applied. As the solvent evaporates, theexcess composition hardens to form excess coating at and around thecontact points between the stent and the supporting apparatus. Upon theremoval of the coated stent from the supporting apparatus, the excesscoating may stick to the apparatus, thereby removing some of the neededcoating from the stent and leaving bare areas. Alternatively, the excesscoating may stick to the stent, thereby leaving excess coating as clumpsor pools on the struts or webbing between the struts.

Thus, it is desirable to minimize the influence of the interface betweenthe stent and the supporting apparatus during the coating process toreduce or eliminate coating defects. As indicated above, the interfaceor contact points between a stent support and the stent can lead todefects. This is particularly the case where the support and the stenthave 1:1 rotation, and thus, do not move relative to one another duringthe coating process. The lack of relative movement can lead tostationary contact points caused by the stent adhering to the support ata point of contact.

The contact area between a support and stent can be minimized when thesupport has a different axis of rotation than the stent. As describedabove, the ends of a stent can be supported loosely over tapered endssuch as cones. Thus, as the mandrel rotates, the contact pointscontinuously change. Even in this approach, the stent can stick to thesupport members, resulting in stationary contact points.

Embodiments of the present invention include shifting or changing thecontact points of a stent during a coating process to minimize thecoating defects at the contact points. As shown in FIG. 2, stent gripperplates 250 and 252 provide a mechanism to steadily hold the stent onstent support assembly 222 to enable the stent support assembly to movethe contact points of the stent with the stent support assembly. FIG.12A depicts a close-up view of stent gripper plates 250 and 252 fromFIG. 2 positioned below stent 1123 disposed over core wire 1106. Stentgripper plates 250 and 252 are disposed at a distance L from oneanother, the distance L being greater than the outside diameter of astent that is being coated. Stent gripper plates 250 and 252 can beshifted toward each other as shown by arrows 1206 and 1208 and upwardstowards a stent support assembly positioned above stent grippers 250 and252.

Upon drying of a stent, stent gripper plates 250 and 252 are firstshifted upwards to the stent support assembly so that stent 1123 isbetween stent gripper plates 250 and 252, as depicted in FIG. 12B. Therotation of the stent support assembly is stopped so that stent 1123 isnot rotating. Stent gripper plates 250 and 252 then move towards oneanother as shown by arrows 1206 and 1208. As depicted in FIG. 12C, stentgrippers 250 and 252 move close to each other to a predetermined gapwhich will hold stent 1123 stationary while stent support assemblyrotates with respect to stent 1123, as shown by an arrow 1214. The stentsupport assembly can be rotated or clocked just enough to move anycontact points between stent 1123 and any part of the stent supportassembly, for example, less than 5°. Alternatively, the stent supportassembly can be rotated greater than 5°, 10°, 30°, 60°, 90°, 270°, orgreater than 360°. In addition, the stent support assembly can berotated clockwise or counter-clockwise. The rotating or clocking can beuni-directional or bi-directional. For example, the mandrel can beclocked back and forth one or more times.

There are alternative methods of moving contact points or breakingstationary contact points between a stent and a support. In oneembodiment, a stent support can be vibrated to break stationary contactpoints. For example, an ultrasonic device such as a transducer can beused to vibrate a stent support or stent grippers. In anotherembodiment, a stream or puff of air can be directed at a stent mountedon a support to disturb stationary contact points.

Stent and Coating Materials

A non-polymer substrate for an implantable medical device may be made ofa metallic material or an alloy such as, but not limited to, cobaltchromium alloy (ELGILOY), stainless steel (316L), high nitrogenstainless steel, e.g., BIODUR 108, cobalt chrome alloy L-605, “MP35N,”“MP20N,” ELASTINITE (Nitinol), tantalum, nickel-titanium alloy,platinum-iridium alloy, gold, magnesium, or combinations thereof.“MP35N” and “MP20N” are trade names for alloys of cobalt, nickel,chromium and molybdenum available from Standard Press Steel Co.,Jenkintown, Pa. “MP35N” consists of 35% cobalt, 35% nickel, 20%chromium, and 10% molybdenum. “MP20N” consists of 50% cobalt, 20%nickel, 20% chromium, and 10% molybdenum.

In accordance with one embodiment, the coating composition can include asolvent and a polymer dissolved in the solvent and optionally a wettingfluid. The composition can also include active agents, radiopaqueelements, or radioactive isotopes. Representative examples of polymersthat may be used as a substrate of a stent or coating for a stent, ormore generally, implantable medical devices include, but are not limitedto, poly(N-acetylglucosamine) (Chitin), Chitosan,poly(-hydroxyvalerate), poly(lactide-co-glycolide),poly(3-hydroxybutyrate), poly(4-hydroxybutyrate),poly(3-hydroxybutyrate-co-3-hydroxyvalerate), polyorthoester,polyanhydride, poly(glycolic acid), poly(glycolide), poly(L-lacticacid), poly(L-lactide), poly(D,L-lactic acid), poly(D,L-lactide),poly(L-lactide-co-D,L-lactide), poly(caprolactone),poly(L-lactide-co-caprolactone), poly(D,L-lactide-co-caprolactone),poly(glycolide-co-caprolactone), poly(trimethylene carbonate), polyesteramide, poly(glycolic acid-co-trimethylene carbonate),co-poly(ether-esters) (e.g. PEO/PLA), polyphosphazenes, biomolecules(such as fibrin, fibrinogen, cellulose, starch, collagen and hyaluronicacid), polyurethanes, silicones, polyesters, polyolefins,polyisobutylene and ethylene-alphaolefin copolymers, acrylic polymersand copolymers, vinyl halide polymers and copolymers (such as polyvinylchloride), polyvinyl ethers (such as polyvinyl methyl ether),polyvinylidene halides (such as polyvinylidene chloride),polyacrylonitrile, polyvinyl ketones, polyvinyl aromatics (such aspolystyrene), polyvinyl esters (such as polyvinyl acetate),acrylonitrile-styrene copolymers, ABS resins, polyamides (such as Nylon66 and polycaprolactam), polycarbonates, polyoxymethylenes, polyimides,polyethers, polyurethanes, rayon, rayon-triacetate, cellulose acetate,cellulose butyrate, cellulose acetate butyrate, cellophane, cellulosenitrate, cellulose propionate, cellulose ethers, and carboxymethylcellulose. Additional representative examples of polymers that may beespecially well suited for use in fabricating embodiments of implantablemedical devices disclosed herein include ethylene vinyl alcoholcopolymer (commonly known by the generic name EVOH or by the trade nameEVAL), poly(butyl methacrylate), poly(vinylidenefluoride-co-hexafluoropropene) (e.g., SOLEF 21508, available from SolvaySolexis PVDF, Thorofare, N.J.), polyvinylidene fluoride (otherwise knownas KYNAR, available from ATOFINA Chemicals, Philadelphia, Pa., or Kynar2750, available from Arkema), ethylene-vinyl acetate copolymers,poly(vinyl acetate), styrene-isobutylene-styrene triblock copolymers,and polyethylene glycol.

“Solvent” is defined as a liquid substance or composition that iscompatible with the polymer and is capable of dissolving the polymer atthe concentration desired in the composition. Examples of solventsinclude, but are not limited to, dimethylsulfoxide (DMSO), chloroform,acetone, water (buffered saline), xylene, methanol, ethanol, 1-propanol,tetrahydrofuran, 1-butanone, dimethylformamide, dimethylacetamide,cyclohexanone, ethyl acetate, methylethylketone, propylene glycolmonomethylether, isopropanol, isopropanol admixed with water, N-methylpyrrolidinone, toluene, and combinations thereof.

A “wetting” of a fluid is measured by the fluid's capillary permeation.Capillary permeation is the movement of a fluid on a solid substratedriven by interfacial energetics. Capillary permeation is quantified bya contact angle, defined as an angle at the tangent of a droplet in afluid phase that has taken an equilibrium shape on a solid surface. Alow contact angle means a higher wetting liquid. A suitably highcapillary permeation corresponds to a contact angle less than about 90°.Representative examples of the wetting fluid include, but are notlimited to, tetrahydrofuran (THF), dimethylformamide (DMF), 1-butanol,n-butyl acetate, dimethylacetamide (DMAC), and mixtures and combinationsthereof.

Examples of radiopaque elements include, but are not limited to, gold,tantalum, and platinum. An example of a radioactive isotope is p³².Sufficient amounts of such substances may be dispersed in thecomposition such that the substances are not present in the compositionas agglomerates or flocs.

Active Agents

Examples of active agents include antiproliferative substances such asactinomycin D, or derivatives and analogs thereof (manufactured bySigma-Aldrich 1001 West Saint Paul Avenue, Milwaukee, Wis. 53233; orCOSMEGEN available from Merck). Synonyms of actinomycin D includedactinomycin, actinomycin IV, actinomycin I₁, actinomycin X₁, andactinomycin C₁. The bioactive agent can also fall under the genus ofantineoplastic, anti-inflammatory, antiplatelet, anticoagulant,antifibrin, antithrombin, antimitotic, antibiotic, antiallergic andantioxidant substances. Examples of such antineoplastics and/orantimitotics include paclitaxel, (e.g., TAXOL® by Bristol-Myers SquibbCo., Stamford, Conn.), docetaxel (e.g., Taxotere®, from Aventis S.A.,Frankfurt, Germany), methotrexate, azathioprine, vincristine,vinblastine, fluorouracil, doxorubicin hydrochloride (e.g., Adriamycin®from Pharmacia & Upjohn, Peapack N.J.), and mitomycin (e.g., Mutamycin®from Bristol-Myers Squibb Co., Stamford, Conn.). Examples of suchantiplatelets, anticoagulants, antifibrin, and antithrombins includeaspirin, sodium heparin, low molecular weight heparins, heparinoids,hirudin, argatroban, forskolin, vapiprost, prostacyclin and prostacyclinanalogues, dextran, D-phe-pro-arg-chloromethylketone (syntheticantithrombin), dipyridamole, glycoprotein IIb/IIIa platelet membranereceptor antagonist antibody, recombinant hirudin, and thrombininhibitors such as Angiomax a (Biogen, Inc., Cambridge, Mass.). Examplesof such cytostatic or antiproliferative agents include angiopeptin,angiotensin converting enzyme inhibitors such as captopril (e.g.,Capoten® and Capozide® from Bristol-Myers Squibb Co., Stamford, Conn.),cilazapril or lisinopril (e.g., Prinivil® and Prinzide® from Merck &Co., Inc., Whitehouse Station, N.J.), calcium channel blockers (such asnifedipine), colchicine, proteins, peptides, fibroblast growth factor(FGF) antagonists, fish oil (omega 3-fatty acid), histamine antagonists,lovastatin (an inhibitor of HMG-CoA reductase, a cholesterol loweringdrug, brand name Mevacor® from Merck & Co., Inc., Whitehouse Station,N.J.), monoclonal antibodies (such as those specific forPlatelet-Derived Growth Factor (PDGF) receptors), nitroprusside,phosphodiesterase inhibitors, prostaglandin inhibitors, suramin,serotonin blockers, steroids, thioprotease inhibitors,triazolopyrimidine (a PDGF antagonist), and nitric oxide. An example ofan antiallergic agent is permirolast potassium. Other therapeuticsubstances or agents which may be appropriate agents include cisplatin,insulin sensitizers, receptor tyrosine kinase inhibitors, carboplatin,alpha-interferon, genetically engineered epithelial cells, steroidalanti-inflammatory agents, non-steroidal anti-inflammatory agents,antivirals, anticancer drugs, anticoagulant agents, free radicalscavengers, estradiol, antibiotics, nitric oxide donors, super oxidedismutases, super oxide dismutases mimics,4-amino-2,2,6,6-tetramethylpiperidine-1-oxyl (4-amino-TEMPO),tacrolimus, dexamethasone, ABT-578, clobetasol, cytostatic agents,prodrugs thereof, co-drugs thereof, and a combination thereof. Othertherapeutic substances or agents may include rapamycin and structuralderivatives or functional analogs thereof, such as40-O-(2-hydroxy)ethyl-rapamycin (known by the trade name of EVEROLIMUS),40-O-(3-hydroxy)propyl-rapamycin,40-O-[2-(2-hydroxy)ethoxy]ethyl-rapamycin, methyl rapamycin, and40-O-tetrazole-rapamycin.

EXAMPLES

The examples and experimental data set forth below are for illustrativepurposes only and are in no way meant to limit the invention. Thefollowing examples are given to aid in understanding the invention, butit is to be understood that the invention is not limited to theparticular materials or procedures of examples.

Tables 1a-d and 2a-d include spray-coating results for a coated stentusing an exemplary spray coating device 200. Tables 1a-d provide coatingresults for an exemplary device referred to as machine 1 and Tables 2a-dprovide coating results for an exemplary device referred to as machine2. Each table represents data for a set of stents. Tables 1a-b and 2a-bare coating results of a poly(butyl methacrylate) (PBMA) primer and 1c-dand 2c-d are coating results for the poly(vinylidenefluoride-co-hexafluoropropene) (PVDF-HFP) drug coating over the primerlayer. The coating weight is in μg. The relative standard deviation(RSD) is used to gauge the applied coating weight consistency per sprayrepetition.

TABLE 1a Spraying results for 8 mm stent for machine 1. Machine 1 (8 mmMedium) Back Actual Coating Actual Mass Sprayer Weight Per Pass Average273.2 4.6 STDev 6.6 0.1 Minimum 262 4.4 Maximum 290 4.8 RSD 2.4%  2.4%Coating Integrity Yield 100%

TABLE 1b Spraying results for 8 mm stent for machine 1. Machine 1 (8 mmMedium) Back Actual Coating Actual Mass Sprayer Weight Per Pass Average272.7 4.5 STDev 7.2 0.1 Minimum 260 4.3 Maximum 288 4.8 RSD 2.6%  2.6%Coating Integrity Yield 95.83%

TABLE 1c Spraying results for 8 mm stent for machine 1. Machine 1 (8 mmMedium) Back Actual Coating Actual Mass Sprayer Weight Per Pass Average1132.9 18.9 STDev 18.7 0.3 Minimum 1082 18.0 Maximum 1166 19.4 RSD 1.7% 1.7% Coating Integrity Yield 90.63%

TABLE 1d Spraying results for 8 mm stent for machine 1. Machine 1 (8 mmMedium) Back Actual Coating Actual Mass Sprayer Weight Per Pass Average1116.3 18.6 STDev 24.3 0.4 Minimum 1076 17.9 Maximum 1162 19.4 RSD 2.2%  2.2% Coating Integrity Yield 100.00%

TABLE 2a Spraying results for 8 mm stent for machine 2. Machine 2 (8 mmMedium) Back Actual Coating Actual Mass Sprayer Weight Per Pass Average275.2 4.59 STDev 4.9 0.08 Minimum 263.0 4.38 Maximum 284.0 4.73 RSD 1.8% 1.8% Coating Integrity Yield 96.15%

TABLE 2b Spraying results for 8 mm stent for machine 2. Machine 2 (8 mmMedium) Back Actual Coating Actual Mass Sprayer Weight Per Pass Average273.2 4.6 STDev 5.3 0.1 Minimum 261 4.35 Maximum 284 4.73 RSD 1.9%  1.9%Coating Integrity Yield 96.15%

TABLE 2c Spraying results for 8 mm stent for machine 2. Machine 2 (8 mmMedium) Back Actual Coating Actual Mass Sprayer Weight Per Pass Average1113.7 18.56 STDev 23.9 0.40 Minimum 1082.0 18.03 Maximum 1167.0 19.45RSD 2.1%   2.1% Coating Integrity Yield 100.00%

TABLE 2d Spraying results for 8 mm stent for machine 2. Machine 2 (8 mmMedium) Back Actual Coating Actual Mass Sprayer Weight Per Pass Average1098.0 18.3 STDev 17.2 0.3 Minimum 1071 17.85 Maximum 1133 18.88 RSD1.6%  1.6% Coating Integrity Yield 96.43%

Tables 3a-b include spraying and drying parameters used to obtain theabove coating results. Table 3a provides examples showing the sprayingprocess parameters for applying primer and drug coating. Table 3b showsan example of some common process parameters used in applying the primerand drug coating.

TABLE 3a Coating parameters used in coating device. Drug coat ParameterDescription Primer Coat polymer IVEK Pump rate, ml/hr 5 7.5 Atomizationair flow, LPM 12 12 Drying gas flow, LPM 110 110 Number of passes 15 40# of spray passes per dry 3 3 cycle

TABLE 3b Coating parameters used in coating device. ParameterDescription Parameter Value Spindle Rotation Speed, rpm 150 Spraytranslation speed, mm/s 16 Drying Time, second 10 Drying Temp, ° C. 45Nozzle Start Position, mm 10 Nozzle End Position, mm 10

FIGS. 13-17 are Scanning Electron Microscope images of a stent coatedwith an exemplary coating device 200. As above, the stent was coatedwith PBMA primer and PVDF-HFP. FIG. 13 depicts the U-crown of the coatedstent. FIG. 14 depicts the proximal end of the coated stent. FIG. 15depicts the overall coating quality of the coated stent. FIG. 16 depictsthe distal end of the coated stent. FIG. 17 depicts a close-up view(400X high magnification) of the end ring.

While particular embodiments of the present invention have been shownand described, it will be obvious to those skilled in the art thatchanges and modifications can be made without departing from thisinvention in its broader aspects. Therefore, the appended claims are toencompass within their scope all such changes and modifications as fallwithin the true spirit and scope of this invention.

What is claimed is:
 1. A support assembly for supporting a stent duringcoating comprising: a first support element coupled to a rotatablespindle; a support wire, wherein a proximal end segment of the supportwire extends from and is coupled to the first support element; and aclamping device supporting a distal end segment of the support wire,wherein the proximal end segment and the distal end segment of the ofthe support wire are positioned so that the support wire rotatesconcentrically with the first support element when the first supportelement is rotated by the rotatable spindle, and wherein the supportwire rotates relative to the clamping device wherein the clamping devicecomprises arms that are movably coupled to each other such that thesupport wire is secured by the arms when the arms move toward eachother.
 2. The support assembly of claim 1, wherein the clamping devicecomprises arms that are movably coupled to each other such that thesupport wire is secured by the arms when the arms rotate inward movetoward each other.
 3. The support assembly of claim 2, wherein the armseach include a cut-out section, the cut-out sections configured toreceive the support wire when the arms move toward each other.
 4. Thesupport assembly of claim 1, wherein a portion of the first supportelement is configured to support a first end of a stent.
 5. The supportassembly of claim 4, further comprising a second support element coupledto the support wire at a location between the first support element andthe clamping device, wherein a portion of the second support element isconfigured to support a second end of the stent.
 6. The support assemblyof claim 5, wherein the portion of the first support element is a firstcone configured to support the first end of the stent, and the portionof the second support element is a second cone configured to support thesecond end of the stent.
 7. The support assembly of claim 1, wherein thefirst support element is movable into and out of the rotatable spindle.8. The support assembly of claim 6, wherein the support wire is movableinto and out of the clamping device.